We propose to examine the role of genetic factors, diet and environmental exposures in the risk of nonmalignant respiratory disease in a cohort of over 50,000 older adults of Chinese ethnicity in Singapore. We are expanding the scope of a cohort established to examine the relation between diet and cancer. This NCI funded study (an outstanding investigator award to Dr. Yu) includes detailed dietary information using a dietary instrument developed for and validated in this population of Singaporeans of Chinese ethnicity. Follow-up, funded by NCI, includes a telephone interview followed by collection of blood and urine. To expand the capability of the cohort to the study of chronic bronchitis and asthma, questions are being added to the follow-up to determine symptoms of chronic bronchitis, dyspnea and asthma. In addition, smoking data has been expanded to include early and adult life exposure to environmental tobacco smoke and information on nondaily active smoking. Over the next 4 years as follow-up of the cohort is completed, we will be able to conduct epidemiologic analyses to examine exposure that may influence the risk of nonmalignant respiratory disease in adults including tobacco smoking exposure and cooking practices and to examine the possible protective effect of a dietary factors such as antioxidants and isothiocyanates. Genetic polymorphisms for these conditions can be examined in nested case-control samples. This population is of particular interest because the Chinese women in Singapore and elsewhere have been reported to have high rates of chronic bronchitis in the face of low levels of smoking. We foresee this study as the first step in examining genetic and environmental risk factors for adult nonmalignant respiratory disease in low and high risk populations across the world. Enrollment of subjects has begun. Over 10,000 subjects have been administered a follow-up questionnaire and biologic samples are being collected. This is a long term study which will require several years to complete.